INFO - on rheumatoid factor (RF)

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University of Washington

Dr. Gardner

Rheumatoid Factor

History - In the early 1900's, Billings hypothesized the rheumatoid

arthritis (RA) was due to chronic focal infection and Cecil later concluded

in 1929 that RA was secondary to streptococcal infection. He felt that

streptococcal bacteria could be isolated from the blood or joints of 2/3 of

patients with RA and that the serum of patients with RA could agglutinate

suspensions of streptococcal bacteria. Dawson could not reproduce the

bacteriologic findings of Cecil and discovered that serum for RA patients

could agglutinate suspensions of other bacteria as well as streptococci.

Waalar found that sera from RA patients were able to agglutinate sheep red

cells to which anti-sheep red cell serum had been added. This observation

was furthered by Rose and Ragan who in 1948 developed it into a diagnostic

test for RA. Singer and Plotz in 1956 introduced latex particles coated with

human gamma globulin.

Methodology - Latex agglutination testing is still widely used although it

is being supplanted by other methods including ELISA and nephelometry that

are capable of being done by machine rather than by hand to hopefully

improve standardization and reproducibility. Nephelometry uses laser light

scatter to measure the formation of immune complexes in this case,

rheumatoid factor and human IgG.

Mechanism - Most assays detect an IgM antibody that is directed against the

Fc portion of IgG. ELISA testing is capable of detecting other classes of

rheumatoid factors (IgG, IgA) but these are not widely used clinically.

Range - The latex test is reported in a titer with most labs considering >

1:40 as positive. The nephelometry test is usually reported in international

units and the normal range is dependent on the specific laboratory usually <

20 IU.

Utility - Rheumatoid factor is not sensitive nor specific enough to rule in

or out rheumatoid arthritis. The rheumatoid factor is present in 70-80% of

patients who have RA. This means that 20-30% of patients with RA are

seronegative for rheumatoid factor. It is most useful as a prognostic

indicator in patients with RA. People with RA who are rheumatoid factor

positive typically have a more aggressive disease. It is also useful in

confirming one's clinical impression that a polyarthritis that looks like RA

is even more likely to be RA. It is also followed in patients with Sjogren's

disease to predict the development of lymphoma. Rheumatoid factor production

may be a way for the immune system to enlarge immune complexes to make them

more easily removed by the spleen and other immune organs.

There are a variety of other clinical conditions that are characterized by

the presence of rheumatoid factor, limiting its specificity.

Occurrence of Rheumatoid Factor in Other Conditions

Rheumatological Diseases

Rheumatoid Arthritis

SLE

Sjogren's Syndrome

Mixed Connective Tissue Disease

Myositis

Cryoglobulinemia

Infectious Diseases

SBE

Tuberculosis

Syphilis

Chronic hepatitis -- especially Hepatitis C

Leprosy

Kala-azar

Other

Normal aging individuals

Idiopathic pulmonary fibrosis

Cirrhosis

Sarcoidosis

Waldenstrom's Macroglobulinemia

Schmerling and Delbanco recently reported on the results of 563 rheumatoid

factor determinations in an inpatient unit of a large university hospital.

477 of these were negative and 86 were positive. Of the positives, 21 had

RA, 8 others had another rheumatic disease, and 57 were felt to be false

positives. Overall, rheumatoid factor had a low (.24) positive predictive

value for RA or any rheumatic disease (.34) but a high negative predictive

value for RA (.89) and other rheumatic diseases (.85). Thus like many

rheumatological tests, a negative test may be more helpful than a positive

result. The cost was 563 dollars per true positive.

http://uwcme.org/site/courses/legacy/rheumlab/rafactor.php

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Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org